Comparative cardiovascular safety of dementia medications: A cross-national study

Objectives To compare the cardiovascular safety of currently marketed dementia medications in new users in the United States and Denmark. Design Retrospective cohort study. Setting Nationally representative sample of Medicare beneficiaries from 2006 through 2009 and nationwide Danish administrative registries from 1997 through 2007. Participants Individuals treated with a dementia medication aged 65 and older. Measurements Hospitalizations for myocardial infarction (MI), heart failure, and syncope or atrioventricular block in both cohorts; fatal or nonfatal MI and cardiac death in the Danish cohort; and all-cause mortality in sensitivity analyses. Results In 46,737 Medicare beneficiaries and 29,496 Danish participants, donepezil was the most frequently used medication. There were no substantial differences in the risk of MI or heart failure between participants using donepezil and those using other cholinesterase inhibitors (all hazard ratios (HR) crossing 1). In the Danish cohort, memantine was associated with fatal or nonfatal MI (HR = 1.33, 95% confidence interval (CI) = 1.08-1.63), cardiac death (HR = 1.31, 95% CI = 1.12-1.53), and a trend toward higher rates of hospitalization for MI (HR = 1.31, 95% CI = 0.98-1.76). Memantine was also associated with greater risk of all-cause mortality in the Medicare (HR = 1.20, 95% CI = 1.13-1.28) and Danish (HR = 1.83, 95% CI = 1.73-1.94) cohorts, suggesting that sicker individuals were selected for memantine therapy. Conclusion Cholinesterase inhibitors have similar cardiovascular risk profiles. Associations between memantine and fatal outcomes in Denmark may be related, in part, to selection of sicker individuals for memantine therapy.